1. Field of the Invention
The present invention relates to hybrid plasminogen activator-like polypeptides, and a process for production thereof using genetic engineering. The hybrid plasminogen activator-like polypeptides according to the present invention can be used for the prevention and treatment of various kinds of cardiovascular disorders or diseases.
2. Description of the Related Art
Plasminogen activator hydrolyses, in a limited fashion, inactive-type enzyme plasminogen present in plasma, to convert it into active-type enzyme plasmin. The plasmin can hydrolyse fibrin clots generated in a blood vessel and resulting in lysis of thrombus, i.e., fibrinolysis. Since the plasmin is rapidly inactivated in vivo by a plasmin inhibitor present in plasma, a plasminogen activator is clinically used as a thrombolytic agent.
As a plasminogen activator, at present, urokinase isolated from human urine is clinically used. However, urokinase has a disadvantage in that, when administered in a large amount, it can result in systemic hemorrhage. The systemic hemorrhage depends on the ratio of fibrinogen-degradation activity and fibrin-degradation activity of the plasminogen activator. Namely, the systemic hemorrhage depends on the affinity of the plasminogen activator to fibrin. Therefore, attempts have been made to produce urokinase having an affinity to fibrin.
On the other hand, a tissue plasminogen activator has a high affinity to fibrin, and therefore, has been considered as a replacement for urokinase. However, the tissue plasminogen activator has an enzyme activity lower than the urokinase, and is less stable in the blood.
Therefore, there is a demand for a new type of plasminogen activator having a satisfactory affinity to fibrin and a sufficient enzyme activity, as well as a satisfactory stability in vivo.